A Prime/Boost Vaccine Regimen Alters the Rectal Microbiome and Impacts Immune Responses and Viremia Control Post-Simian Immunodeficiency Virus Infection in Male and Female Rhesus Macaques.
AIDS Vaccines
/ immunology
Adenoviridae
/ genetics
Animals
Female
Immunity, Humoral
Immunity, Mucosal
Immunization, Secondary
/ methods
Macaca mulatta
/ immunology
Male
Microbiota
/ drug effects
Rectum
/ immunology
SAIDS Vaccines
/ immunology
Simian Acquired Immunodeficiency Syndrome
/ immunology
Simian Immunodeficiency Virus
/ immunology
Viremia
/ immunology
SIV vaccine
cellular immunity
humoral immunity
microbiome
mucosal and systemic immunization
rhesus macaque
Journal
Journal of virology
ISSN: 1098-5514
Titre abrégé: J Virol
Pays: United States
ID NLM: 0113724
Informations de publication
Date de publication:
23 11 2020
23 11 2020
Historique:
received:
17
06
2020
accepted:
15
09
2020
pubmed:
25
9
2020
medline:
26
1
2021
entrez:
24
9
2020
Statut:
epublish
Résumé
An efficacious human immunodeficiency virus (HIV) vaccine will likely require induction of both mucosal and systemic immune responses. We compared the immunogenicity and protective efficacy of two mucosal/systemic vaccine regimens and investigated their effects on the rectal microbiome. Rhesus macaques were primed twice mucosally with replication-competent adenovirus type 5 host range mutant (Ad5hr)-simian immunodeficiency virus (SIV) recombinants and boosted twice intramuscularly with ALVAC-SIV recombinant plus SIV gp120 protein or with DNA for SIV genes and rhesus interleukin-12 plus SIV gp120 protein. Controls received empty Ad5hr vector and alum adjuvant only. Both regimens elicited strong, comparable mucosal and systemic cellular and humoral immunity. Prevaccination rectal microbiomes of males and females differed and significantly changed over the course of immunization, most strongly in females after Ad5hr immunizations. Following repeated low-dose intrarectal SIV challenges, both vaccine groups exhibited modestly but significantly reduced acute viremia. Male and female controls exhibited similar acute viral loads; however, vaccinated females, but not males, exhibited lower levels of acute viremia, compared to same-sex controls. Few differences in adaptive immune responses were observed between the sexes. Striking differences in correlations of the rectal microbiome of males and females with acute viremia and immune responses associated with protection were seen and point to effects of the microbiome on vaccine-induced immunity and viremia control. Our study clearly demonstrates direct effects of a mucosal SIV vaccine regimen on the rectal microbiome and validates our previously reported SIV vaccine-induced sex bias. Sex and the microbiome are critical factors that should not be overlooked in vaccine design and evaluation.
Identifiants
pubmed: 32967951
pii: JVI.01225-20
doi: 10.1128/JVI.01225-20
pmc: PMC7925174
pii:
doi:
Substances chimiques
AIDS Vaccines
0
SAIDS Vaccines
0
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2020 American Society for Microbiology.
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